The epidermal growth factor receptors (EGFR) belong to the ErbB family of receptor tyrosine kinases (RTK) and participate in the regulation of cellular homeostasis such as cell proliferation, apoptosis, migration, survival and complex processes including angiogenesis and tumorigenesis (Wheeler, D. L.; et al. Nat. Rev. Clin. Oncol. 2010, 7, 493.). It has been established that dysregulated EGFR expression and signaling play a critical role in the etiology of human cancers (Ullrich, A.; et al. Nature 1984, 309, 418. Veale, D.; et al. Brit. J. Cancer 1987, 55, 513. Weichselbaum, R. R.; et al. Head Neck 1989, 11, 437).
Lung cancer is the leading cause of cancer-related mortality worldwide. Despite recent advances in medical and surgical therapies, the improvement in lung cancer mortality due to current treatments remains unsatisfactory. Recently, specific targeted therapies for lung cancer have been developed rapidly. One of these targeted therapies, the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), was successfully implemented for lung cancer therapy owing to the prevalence of EGFR mutations in non-small cell lung cancer (NSCLC).
However, most patients eventually develop acquired resistance to the therapy after approximately one year on this therapy. Therefore, there is an urgent need to develop new anti-cancer drugs that effectively treat lung cancer.
Breast cancer is a heterogeneous disease that often occurs in the pre- and post-menopause period of women. Most breast cancer cells, such as MCF, are sensitive to estrogen receptor (ER) and progesterone receptor (PR) with overexpression of human epidermal growth factor receptor 2 (HER2). (Subik, K.; et al. Breast Cancer: Basic Clin. Res. 2010, 4, 35-41. Holliday D. L. & Speirs, V. Breast Cancer Res. 2011, 13, 215. Beelen, K.; et al. Nat. Rev. Clin. Oncol. 2012, 9, 529-541.) In contrast, MDA-MB-231 cell is a triple-negative breast cancer (TNBC) cell because it has low expression of HER2 and no expression of ER or PR. Prognosis and treatment of TNBCs are difficult since most drugs only target one of the three receptors. To develop therapeutic agents for treatment of TNBC patients is also especially important.